Health-related quality of life in patients aged 6-18 years with chronic hepatitis C treated with sofosbuvir/velpatasvir.

BACKGROUND & AIMS: The aim of this study was to assess the effect of treatment with sofosbuvir/velpatasvir (SOF/VEL) on the health-related quality of life (HRQL) of children with chronic hepatitis C. METHODS: In the non-commercial, non-randomized, open-label PANDAA-PED study, 50 children aged 6-18 years with chronic hepatitis C were treated with a fixed dose of SOF/VEL. All patients achieved sustained virologic response 12 weeks after the end of treatment (SVR12). Evaluation of HRQL was performed twice: at baseline (before the treatment) and during the SVR12 analysis using the KIDSCREEN-27 questionnaires, which included 5 dimensions of HRQL, for child self-reporting and parent proxy reporting. The normal range for the population was set to T values of 50 ± 10 points. Child-parent agreement was analysed using the intra-class correlation coefficient (ICC) and Bland-Altman test. RESULTS: Mean T values were within the normal range for all dimensions, both before and after treatment. There was a significant improvement in physical well-being based on the children's self-assessment (from 48.53 to 51.21, p = .03). In addition, a trend towards better scores in the 'social support & peers' part of the parent proxy evaluation (from 45.98 to 48.66, p = .06) was noticed. After the treatment, the proportion of children self-assessing their physical well-being as below normal significantly decreased from 17% to 5% (p = .007). HRQL scores were not associated with patients' sex, but in most cases, younger age correlated with better HRQL. Evaluation of the ICC for child self-reports versus parent proxy reports revealed poor to moderate agreement for most single measures. Bland-Altman analysis showed that in all dimensions, both before and after treatment, the limits of agreement (LoAs) exceeded ±5 points (half of the SD and considered a maximum allowed difference). CONCLUSIONS: A significant proportion of children with chronic hepatitis C have decreased HRQL in all dimensions, but effective treatment with SOF/VEL leads to an improvement in some areas of well-being. As the effect of HCV on HRQL is more pronounced in older patients, treatment of younger children should be indicated to prevent them from experiencing decreased HRQL due to ongoing HCV infection in the future.

Ukrainian War Refugee Children With Particularly Severe Viral Infections: A Case Series Report.

The humanitarian crisis in Ukraine in 2022 led to a massive migration of refugees to Poland. Immigrant children, living in overcrowded humanitarian hubs, were exposed to multiple stressful factors likely affecting their immune systems. This case series study aimed to describe a particularly severe course of common viral infections, in Ukrainian refugee children. We present 2 case series of Ukrainian refugee children: 5 hospitalized due to either adenovirus (AdV) and 8 with rotavirus (RV) infection, admitted within 3 months in each case series, recruited retrospectively. Most patients lived in humanitarian hubs and were neglected on admission (dehydrated, with poor hygiene and anxious). All RV infection cases had symptoms of severe gastroenteritis requiring intravenous rehydration. Metabolic acidosis was present in 6 children, and hypoglycemia in 4 participants. None of them were vaccinated against RV. All children with AdV infection had prolonged fever, dyspnea requiring oxygen therapy and hyperinflammation. In 2 AdV infection cases with no clinical improvement and increasing inflammatory markers, intravenous immunoglobulins and glucocorticosteroids were used. The combination of stressful factors and living in overcrowded hubs during the high prevalence of viral infections led to a particularly severe course of viral infections in Ukrainian refugee children.

Efficacy and safety of treatment with sofosbuvir/velpatasvir in patients aged 6-18 years with chronic hepatitis C-Results of the PANDAA-PED study.

BACKGROUND AND AIMS: The aim of this non-commercial, open-label, real-life, non-randomized clinical trial was to analyse the efficacy and safety of a pangenotypic regimen sofosbuvir/velpatasvir (SOF/VEL) in patients aged 6-18 years with chronic hepatitis C virus (HCV) infection. METHODS: Fifty patients qualified for the 12-week treatment were divided into two weight groups: 15 children weighting between 17 and <30 kg received a fixed dose of 200/50 mg of SOF/VEL (tablet) once daily, and 35 patients weighting ≥30 kg were treated with 400/100 mg SOF/VEL. The primary endpoint of the study was efficacy defined as sustained viral response (undetectable HCV RNA using an real-time polymerase chain reaction method) at 12 weeks posttreatment (SVR12). RESULTS: Median age of the participants was 10 (IQR 8-12) years, 47 were infected vertically, and 3 patients were previously ineffectively treated with pegylated interferon and ribavirin. Thirty-seven participants were infected with HCV genotype 1, 10 with HCV genotype 3 and the remaining 3 with genotype 4. There was no case of cirrhosis. SVR12 was 100%. Thirty-three reported adverse events (AEs) were considered related to the administration of SOF/VEL, all of them were mild or moderate. Children presenting with AEs were older compared to these without AEs: 12 (9.5-13) versus 9 (IQR 8-11) years (p = 0.008). CONCLUSIONS: Results of the PANDAA-PED study indicated a 100% effectiveness of a 12-week therapy with SOF/VEL in children aged 6-18 years with chronic HCV infection and its good safety profile, in particular in younger patients.

Online Self-Disclosure and Social Sharing of Emotions of Women with Breast Cancer Using Instagram-Qualitative Conventional Content Analysis.

OBJECTIVES: Women with breast cancer share their experiences and emotions about the illness on Instagram - a tool understudied when it comes to chronic illness. The paper characterizes the women's activities, and both online self-disclosure and social sharing of emotions concepts are used to help explain the women's practices. METHODS: Using qualitative conventional content analysis, four profiles of women are manually analysed, with posts as the unit of analysis (n = 811). Based on eleven subcategories, three broad analytical categories are introduced: self-disclosure of negative information (C1), self-disclosure of positive information (C2) and disclosure of information about other people (C3). RESULTS: The women post narratives about suffering resulting from cancer, and the fears they experience. Also, the posts relate to positive emotions, joyful life events, self-acceptance, or self-affirmation. While writing, the women share information about people supporting them on their way to recovery. DISCUSSION: The activity of women cannot be explained only by their online self-disclosure, where anonymity and lack of offline support are often emphasized. Women on Instagram are not anonymous and report on support by relatives and other people. Rimé's concept of social sharing of emotions is used to explain this phenomenon.

Pegylated interferon and ribavirin gone but not forgotten in the era of direct-acting antivirals.

BACKGROUND: Therapy with pegylated interferon and ribavirin (PEG-IFN+RBV) for chronic hepatitis C (CHC) remains the only option available for children in many Eurasian and European countries. Our aim was to evaluate the influence of host and viral factors on response to IFN-based therapy to optimize it for those in whom directly acting antivirals (DAA) are currently unavailable. METHODS: Seventeen vertically infected, treatment naive children (10 male and 7 female) aged 5-16 years with CHC underwent a course of PEG-IFN+RBV. The end point was sustained virologic response (SVR). Host and virus factors were divided into pre- and on-treatment predictors of response to therapy. RESULTS: Eleven patients obtained SVR (64%), 4 were non-responders (23%), and 2 were relapsers (12%). Significant relationship was found between HCV RNA elimination and following variables: virus genotype and early virologic response (EVR) (P<0.037, P<0.029 respectively). Higher eradication rate was observed in patients infected with genotype 3 HCV (100% vs. 65% with genotype 1 or 4), and in those with undetectable HCV RNA by week 12 (88% vs. 66% with viremia). EVR was associated with SVR (83% vs. 0% in nonresponders; P<0.004). C allele of IL28B rs12979860 was a predictor of EVR (P<0.043). The SVR rates among CC, CT, and TT carriers were as follows: 75%, 67%, and 33%. CONCLUSIONS: Detection of favorable HCV and IL28B genotype prior to commencement of PEG-IFN+RBV and continuing it in patients with EVR is of major importance for those in whom DAA are still unavailable.

Acute Hepatitis B and Unusual Follow-Up in a 16-Year-Old Boy: Case Report.

In this case report, we present a 16-year-old Ukrainian boy with acute hepatitis B. He had not been previously vaccinated against hepatitis B. Possible sources of infection included: a tattoo made at home, a finger cut made with hairdresser scissors during work, and unprotected sexual encounters. The clinical course of the disease was typical with jaundice and elevated aminotransferases levels without liver failure. During the follow-up visit 16 months after the onset of the disease, chronic hepatitis b was excluded but an ulcer around his anus was found. Additional tests for sexually transmitted diseases were ordered and they were positive for syphilis. The extended interview revealed that the patient had several unprotected bisexual encounters, which may have indicated a potential source of infections including the hepatitis B virus (HBV). The reported case shows that despite the significant decrease in the hepatitis B prevalence in Poland, the infection is still possible. It is necessary to conduct epidemiological interviews regarding sexually transmitted diseases in teenagers, especially when a blood-borne disease has been diagnosed.

Progress and Barriers Towards Elimination of Chronic Hepatitis C in Children.

Chronic hepatitis C (CHC) is a global health burden. Mother-to-child transmission (MTCT) accounts for most HCV infections in pediatric patients. Spontaneous viral clearance may occur in early childhood but is uncommon thereafter. Infection is usually asymptomatic during childhood, although without an effective treatment, vertically infected children may develop serious liver complications including cirrhosis and hepatocellular carcinoma in adulthood. Despite the lack of vaccine against hepatitis C and effective post-exposure methods of prevention of MTCT, treatment with direct-acting antiviral agents (DAAs) raised the prospect of eliminating HCV on a population level. Highly effective, well-tolerated, oral, and interferon-free regimens of short duration have revolutionized treatment of CHC. However, access to these therapies might be limited because of its high cost. In this review, we provide the current state of knowledge on the epidemiology, testing, monitoring and treating of HCV in children. We outline the remaining gaps in therapy and barriers to disease eradication.

On a straight path to HCV elimination in children - new prospects for hepatitis C treatment in Poland.

Difficulties in achieving elimination targets of the World Health Organization's Global Strategy on viral hepatitis might be overcome through a new micro-elimination approach that allows for a quick, efficient targeting of treatment and prevention services. Particular focus on identification of high-risk and so far marginalized populations, such as children and adolescents, increases chances for HCV elimination on a country, and ultimately on a population level. Therefore, a broad access to safe and highly effective direct-acting antiviral drugs is of upmost importance in the pediatric population.

A red tide in the pack ice of the Arctic Ocean.

In the Arctic Ocean ice algae constitute a key ecosystem component and the ice algal spring bloom a critical event in the annual production cycle. The bulk of ice algal biomass is usually found in the bottom few cm of the sea ice and dominated by pennate diatoms attached to the ice matrix. Here we report a red tide of the phototrophic ciliate Mesodinium rubrum located at the ice-water interface of newly formed pack ice of the high Arctic in early spring. These planktonic ciliates are not able to attach to the ice. Based on observations and theory of fluid dynamics, we propose that convection caused by brine rejection in growing sea ice enabled M. rubrum to bloom at the ice-water interface despite the relative flow between water and ice. We argue that red tides of M. rubrum are more likely to occur under the thinning Arctic sea ice regime.

Hepatitis C infection among pregnant women in central Poland: Significance of epidemiological anamnesis and impact of screening tests to detect infection.

BACKGROUND: Mother-to-child transmission is one of the main sources of hepatitis C virus (HCV) infection in children. However, because of the asymptomatic course of the illness, certain women may not be aware of their infection. OBJECTIVES: The aim of this study was to estimate the significance of epidemiological anamnesis in diagnoses of HCV infection in women of reproductive age and to evaluate how screening among pregnant women impacts the detection of HCV infection. MATERIAL AND METHODS: Epidemiological interviews of 432 mothers infected with HCV (but free of human immunodeficiency virus (HIV)) were conducted in the Warsaw Hospital for Infectious Diseases (Poland) from 1998 to 2012. RESULTS: Complaints or abnormalities in laboratory tests were the reasons for anti-HCV antibody testing in 28.2% of mothers, whereas specific interview responses or occupational health care services group affiliation were the reasons for testing in 35.6%. However, in a large group of women, infection was only detected because of screening examinations. The introduction of routine screening for pregnant women (since 2010 in Poland) has led to the increased detection of HCV infection in women who did not present with infection risk factors (9.9% before 2010 vs 46.1% after 2010). This practice has also led to an increase in the percentage of women diagnosed during pregnancy (21.5% before 2010 vs 30.8% after 2010). CONCLUSIONS: Establishing HCV infection risk factors during the interview process is the most common indicator for serological testing; however, not all infected cases can be diagnosed in this manner. Screening for anti-HCV antibodies in pregnant women increases the detection of HCV infection in this group.

Non-invasive evaluation of the liver disease severity in children with chronic viral hepatitis using FibroTest and ActiTest - comparison with histopathological assessment.

AIM OF THE STUDY: Was to evaluate liver disease severity in children with chronic viral hepatitis using the FibroTest and ActiTest (FT/AT), and compare the results with the liver biopsy. MATERIAL AND METHODS: The study included 11 treatment-naïve children [mean age, 9.0 ± 3.0 years, 10 infected with hepatitis C virus (HCV), and 1 with hepatitis B virus (HBV)] who underwent an FT/AT. Ten of the children underwent a liver biopsy. The histopathological evaluation was based on the METAVIR scoring system. The FT/AT and METAVIR scores were considered concordant if the necroinflammatory activity or the fibrosis did not differ by more than one grade or stage. To analyze the agreement between the FT/AT and the histopathological evaluation, the inter-rater agreement (kappa) was used. RESULTS: In the histopathological evaluation, most children presented with mild necroinflammatory activity (METAVIR A1) and with minimal to mild fibrosis (METAVIR F1-2). Both the AT and FT values did not show any linear increases with advancing METAVIR scores A and F, respectively. A discordance between the FT and METAVIR scores was observed in 3/10 (30%) cases; concordance between the AT and METAVIR scores was found in 9/10 cases. The inter-rater agreement test showed poor agreement between the FT/AT and the histopathological evaluation (kappa for AT: 0.0667, and kappa for FT: 0.176). CONCLUSIONS: The FT and AT values poorly correlate with histopathological evaluation. Further studies on non-invasive methods to evaluate liver disease severity in children with chronic viral hepatitis are needed.

Clinical usefulness of new noninvasive serum biomarkers for the assessment of liver fibrosis and steatosis in children with chronic hepatitis C.

AIM OF THE STUDY: Recently, novel serum markers modified by the body mass index z-score (BMI z-score) were proposed as a reliable noninvasive alternative for the detection of significant fibrosis and steatosis in children with chronic hepatitis C (CHC). The aim of this study was to evaluate the clinical usefulness of these biomarkers. MATERIAL AND METHODS: Thirty children aged 9.4 ± 3.7 years (14 males, 16 females) with CHC were included in this study. In all patients, histopathological evaluation of the liver fibrosis was performed using a 5-point METAVIR scoring system (≥ 2 points = significant fibrosis). Significant steatosis was diagnosed with > 33% of hepatocytes affected. The following noninvasive markers of liver disease were calculated: the modified aspartate transaminase (AST)-to-platelet ratio index (M-APRI: BMI z-score × APRI), the modified Fibrosis-4 index (M-FIB-4: BMI z-score × FIB-4), and a novel marker, B-AST (BMI z-score × AST). The clinically useful cut-offs for each marker were selected as simple round numbers, indicating significant fibrosis and steatosis. RESULTS: Significant fibrosis was detected in 7/30 (23%) cases, and significant steatosis was observed in 4 (13%) patients. Comparison with the histopathological evaluation revealed that B-AST < 0 excluded significant fibrosis, and < 100 excluded all patients with significant steatosis. For the M-APRI, < 0 excluded significant fibrosis, and < 0.5 excluded significant steatosis. For the M-FIB-4, < 0 excluded significant fibrosis and < 0.2 excluded significant steatosis. CONCLUSIONS: Negative values of all three markers that included the BMI z-score excluded all patients with both significant fibrosis and significant steatosis.

Novel serum biomarkers modified by the body mass index z-score for the detection of liver fibrosis and steatosis in children with chronic hepatitis C.

BACKGROUND: There is a need for validation of noninvasive alternatives to liver biopsy for the evaluation of fibrosis in children with chronic hepatitis C (CHC). The aim of this study was to evaluate the diagnostic performance of serum biomarkers modified by the body mass index z-score (BMI z-score) for the detection of fibrosis and steatosis in children with CHC. METHODS: Thirty children aged 9.4 ± 3.7 years (14 males, 16 females) with CHC underwent liver biopsy. Fibrosis was scored using a 5-point METAVIR scale (≥2 = significant fibrosis). For all the children, the following noninvasive markers were calculated: The aspartate transaminase (AST)-to-platelets ratio index (APRI), the modified APRI (M-APRI: BMI z-score × APRI), the Fibrosis-4 index (FIB-4), the modified FIB-4 (M-FIB-4: BMI z-score × FIB-4), and a novel marker, B-AST (BMI z-score × AST). The area under the receiver operator characteristic curve (AUROC) was calculated to detect significant fibrosis and steatosis. RESULTS: In the histopathological evaluation, 22/30 (73%) patients presented with fibrosis, and 8/30 (27%) presented with steatosis. For the detection of significant fibrosis, the AUROCs for M-APRI, M-FIB-4 and B-AST were 0.842, 0.823, and 0.848, respectively. For significant steatosis, the AUROCs were more than 0.9 for all markers that included the BMI z-score. B-AST, with a cut-off of 92.8, showed 71% sensitivity and 95% specificity for detecting significant fibrosis. For predicting severe steatosis, B-AST had 100% sensitivity and 92% specificity. Negative values of all three markers that included BMI z-scores excluded all patients with both significant fibrosis and significant steatosis. CONCLUSIONS: Including the BMI z-score in serum biomarker formulas enhances their diagnostic ability to detect significant fibrosis and steatosis. B-AST may thus act as an effective alternative to liver biopsy.

Liver steatosis in children with chronic hepatitis B and C: Prevalence, predictors, and impact on disease progression.

Only scarce data on liver steatosis in children with chronic hepatitis B and C (CHB and CHC) are available. The objective of this study was to evaluate the prevalence, predictors, and impact of hepatic steatosis on children with CHB and CHC. A total of 78 patients aged 11.5 ±â€Š3.4 years were included: 30 (38%) had CHB, and 48 (62%) had CHC. Steatosis was scored on a 5-point scale, as follows: absent; minimal (≤5% hepatocytes affected), mild (6-33%), moderate (34-66%), and severe (>66%). Stepwise logistic regression was used to determine the factors associated with steatosis and moderate-to-severe steatosis. Steatosis was observed in 4/30 (13%) patients with CHB and 13/48 (27%) patients with CHC (P = 0.17). Moderate-to-severe steatosis was observed in 6/78 (8%) patients: 1/30 (3%) had CHB and 5/48 (10%) had CHC (P = 0.40). The body mass index (BMI) z-score was positively associated with the presence of steatosis in children with CHB (odds ratio [OR] = 3.3, 95% confidence interval [CI]: 1.02-10.64). In CHC, steatosis occurred more frequently in patients with hepatitis C virus genotype 3 compared with other genotypes (P = 0.002). In patients with non-3 genotype hepatitis C virus, steatosis was associated with the stage of fibrosis (OR = 3.35, 95% CI: 1.01-11.07) and inversely associated with the duration of infection (OR = 0.74, 95% CI: 0.55-0.97). Moderate-to-severe steatosis was positively associated with the BMI z-score (OR = 3.62, 95% CI: 1.22-10.75) and stage of fibrosis (OR = 3.89, 95% CI: 1.05-14.47). Steatosis is a common finding in children with chronic viral hepatitis. It is associated with metabolic factors in CHB, whereas in patients with CHC, metabolic and viral factors may have a combined effect, leading to more advanced grades of steatosis in children with higher BMI z-scores. Moderate-to-severe steatosis is a predictor of advanced fibrosis in children with CHC.

Predictors of Liver Disease Severity in Children with Chronic Hepatitis B.

BACKGROUND: Evaluation of the liver histology is essential for the management of chronic hepatitis B (CHB) in children. OBJECTIVES: The aim of this study was to analyze the histopathological features in children with CHB and compare them with clinical and laboratory data. MATERIAL AND METHODS: The study comprised 30 treatment-naïve children (mean age: 12.8 ± 2.4; mean duration of infection: 11.7 ± 2.5 years; 16/30 HBeAg-positive and 14/30 HBeAg-negative), who underwent a liver biopsy due to CHB. Liver biopsies were evaluated according to the modified Knodell score. RESULTS: A histopathological evaluation revealed mild to severe necroinflammatory activity (mean grading: 5.4 ± 3.2) and fibrosis (mean staging: 1.7 ± 0.9), irrespective of the HBeAg-status, viral load and duration of infection. One case of cirrhosis was observed. A multiple regression analysis revealed that alanine and aspartate aminotransferase (ALT and AST) levels were associated with the necroinflammatory activity (p = 0.001 for ALT, and p = 0.006 for AST). No such correlation for fibrosis was observed; however, children with elevated AST were prone to more advanced fibrosis compared to children with normal AST level (p = 0.01). CONCLUSIONS: Children with CHB presented a wide range of liver changes over a decade after the infection. The severity of liver lesions did not differ according to the HBeAg status, viral load and duration of the infection. ALT and AST levels correlated positively with the inflammatory activity. AST seems to be a better predictor of fibrosis compared to ALT. Liver biopsy is a useful tool in evaluating the severity of liver disease in children with chronic hepatitis B, whereas clinical and laboratory parameters are weak predictors of liver injury.

Is liver biopsy still needed in children with chronic viral hepatitis?

Liver biopsy is a standard method used for obtaining liver tissue for histopathological evaluation. Since reliable serological and virological tests are currently available, liver biopsy is no longer needed for the etiological diagnosis of chronic hepatitis B and C. However, liver histology remains the gold standard as a prognostic tool, providing information about the liver disease progression (grading of necroinflammatory activity and staging of fibrosis) and serving clinicians in the management and therapeutic decisions. In general, histopathological evaluation is indicated before starting the antiviral treatment. Main limitations of the liver biopsy include its invasive and painful procedure, sampling errors and the inter- and intra-observer variability. In addition, indications for the liver biopsy in pediatric patients with chronic viral hepatitis were questioned recently, and efforts have been made toward the development of non-invasive methods as an alternative to the liver biopsy. The most commonly used methods are novel imaging studies (elastography) and combinations of biomarkers. However, to date, none of these tests was validated in children with chronic viral hepatitis. In this review, we present the current status of the liver biopsy in the management of chronic viral hepatitis B and C in pediatric population, including specific indications, complications, contraindications, problems, limitations, and alternative non-invasive methods.

Determinants of liver disease progression in children with chronic hepatitis C virus infection.

Histopathological features and determinants of liver disease progression were analyzed in 42 treatment-naïve children (mean age: 10.7 ±3.7) with chronic hepatitis C (14/42 infected vertically and 26/42 horizontally). Histopathological evaluation was performed according to Knodell's modified system. Predictors of necroinflammation and fibrosis were identified using linear regression analyses. Most children presented with mild necroinflammation and fibrosis (mean grade 4.3 ±2.7, mean staging 1.2 ±0.8), irrespective of the mode of transmission. Vertically infected children were younger than those infected horizontally (8.6 ±2.5 vs. 11.5 ±3.7 years, p = 0.02). Alanine and aspartate aminotransferase (ALT and AST) levels were associated with necroinflammation (p = 0.003 and p = 0.01 for ALT and AST, respectively) and fibrosis (p = 0.01 and p = 0.04, respectively). Other positive independent predictors of fibrosis included duration of infection (p = 0.03) and body mass index (BMI) z-score (p = 0.03). Children with chronic hepatitis C presented with mild liver changes over a decade after the infection, irrespective of the mode of transmission. Since fibrosis is a time-dependent process, progression of the liver disease in vertically infected children may occur at a younger age compared to patients infected horizontally. Aminotransferase levels were associated with necroinflammation and fibrosis. Longer duration of infection and a higher BMI z-score were associated with more severe fibrosis.